In today’s Science, researchers from the Howard Hughes Medical
Institute and Brown University describe machinery at the synapse for the
synthesis of new proteins that depress synaptic strength. Synaptic weakening is
thought to be a key process in memory creation and
storage.

PROVIDENCE, R.I. — Scientists have identified a novel mechanism behind
the decrease in strength of synapses in the brain, a process that leads to the
creation of memories and their long-term storage.

The increase or decrease in strength among synapses, and subsequent changes
in memory, are based on sensory-driven experiences. Synaptic strengthening or
weakening also occurs during the brain’s development. Synapses are the
connections between neurons, or nerve cells.

Reporting in today’s Science, researchers from the Howard Hughes
Medical Institute (HHMI) and Brown University describe machinery at the synapse
for the synthesis of new proteins that depress synaptic strength. The study was
conducted in rats.

The finding suggests that experience or activity in the mammalian brain can
regulate individual synapses, said lead investigator Kimberly Huber, a
post-doctoral researcher at Brown.

“The study shows that synaptic depression actually relies on the
manufacture of proteins at the synapses,” she said. “This is the
first demonstration in mammals that when synapses change, the modification
depends on new proteins created specifically at the site.”

This synaptic chemical activity is an efficient way for the brain to make new
proteins and change existing ones rapidly, Huber said. “The mechanism
appears to be a viable way for the brain to express its changes. We think this
activity also may be a way that the structure, or shape, of synapses can be
altered.”

The findings hint that connections in the brain can be modified on an
individual basis, facilitating long-term memory storage.

“It is important to understand the mechanism by which connections are
weakened – not only because such understanding may yield insight into
long-term memory, but also because this is a fundamental part of normal brain
development,” said senior investigator Mark Bear, an HHMI investigator and
professor of neuroscience at Brown.

Although synapses have the machinery to make proteins, there had not been
evidence that this machinery can function to change synapses.

Huber and colleagues worked with tissue from the hippocampus region of the
brain, separating synapses from their cell bodies. Even after the cells and
synapses were cut apart, the synapses continued to be modified by local protein
activity, indicating that synaptically synthesized proteins are involved.

This led the researchers to introduce specific inhibitors of the protein
synthetic machinery directly to the synapses. The synaptic depression was
blocked, providing further evidence that the proteins are made at the synapse.
Follow-up experiments, in which the activation of genes at the cell body was
blocked, reinforced that the new proteins are synthesized directly at the
synapses.

The Howard Hughes Medical Institute and a grant from the National Eye
Institute funded the study. The other researcher involved was Matthew Kayser, a
graduating senior who conducted the work as part of his honors thesis.

At Brown, the researchers are based in the Department of Neuroscience in the
School of Medicine. They are currently studying what types of proteins are being
made at the synapses and how experience rapidly regulates synapses through local
protein synthesis.